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Translocation of gut bacteria promotes tumor-associated mortality by inducing immune-activated renal damage. EMBO J. (IF 9.4) Pub Date : 2025-05-22 Fei Cong,Hongcun Bao,Xianfeng Wang,Yang Tang,Yuwei Bao,John S Poulton,Xiaowen Liu,Adam Chun-Nin Wong,Xiang Ji,Wu-Min Deng
Paraneoplastic syndrome represents severe and complex systemic clinical symptoms manifesting in multiple organs of cancer patients, but its cause and cellular underpinnings remain little explored. In this study, establishing a Drosophila model of paraneoplastic syndrome triggered by tumor transplantation, we found that the innate immune response, initiated by translocated commensal bacteria from a
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Inflammatory crosstalk: systemic gut-kidney interplay aggravates tumor host mortality. EMBO J. (IF 9.4) Pub Date : 2025-05-22 Héctor Herranz
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Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence. EMBO J. (IF 9.4) Pub Date : 2025-05-20 Hiroki Sekine,Takaaki Akaike,Hozumi Motohashi
Oxygen and sulfur, both members of the chalcogen group (group 16 elements), play fundamental roles in life. Ancient organisms primarily utilized sulfur for energy metabolism, while the rise in atmospheric oxygen facilitated the evolution of aerobic organisms, enabling highly efficient energy production. Nevertheless, all modern organisms, both aerobes and anaerobes, must protect themselves from oxygen
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Redox regulation of G protein oligomerization and signaling by the glutaredoxin WG1 controls grain size in rice. EMBO J. (IF 9.4) Pub Date : 2025-05-19 Lijie Liu,Jianqin Hao,Ke Huang,Penggen Duan,Baolan Zhang,Zhihai Chi,Xiaohong Yao,Yunhai Li
Grain size is an important agronomic trait and influences both grain yield and quality in crops. The atypical heterotrimeric Gγ protein subunit GS3 is a central regulator of grain length in rice, and the loss-of-function allele of its corresponding gene has been widely utilized by breeders to improve grain length in rice. Here we report that the CC-type glutaredoxin WG1/OsGRX8 has disulfide oxidoreductase
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Early coordination of cell migration and cardiac fate determination during mammalian gastrulation. EMBO J. (IF 9.4) Pub Date : 2025-05-13 Shayma Abukar,Peter A Embacher,Alessandro Ciccarelli,Sunita Varsani-Brown,Isabel G W North,Jamie A Dean,James Briscoe,Kenzo Ivanovitch
During gastrulation, mesodermal cells derived from distinct regions are destined to acquire specific cardiac fates after undergoing complex migratory movements. Here, we used light-sheet imaging of live mouse embryos between gastrulation and heart tube formation to track mesodermal cells and to reconstruct lineage trees and 3D migration paths for up to five cell divisions. We found independent progenitors
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Mechanistic insight into anaphase bridge signaling to the abscission checkpoint. EMBO J. (IF 9.4) Pub Date : 2025-05-12 Manika I Singh,Girish Rajendraprasad,Vasileios Katopodis,Rui Cui,Marin Barisic,Rahul Bhowmick,Ian D Hickson
During cytokinesis in human cells, a failure to resolve persistent DNA bridges that span the cell-division plane maintains the Aurora B-dependent abscission checkpoint in an active state. However, the molecular mechanism by which unresolved sister-chromatid bridging signals to this checkpoint is poorly defined. Here, we define an essential role for the Bloom's syndrome helicase, BLM, in signaling to
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Inhibitors of eIF1A-ribosome interaction unveil uORF-dependent regulation of translation initiation and antitumor and antiviral effects. EMBO J. (IF 9.4) Pub Date : 2025-05-12 Daniel Hayat,Ariel Ogran,Shaked Ashkenazi,Alexander Plotnikov,Roni Oren,Mirie Zerbib,Amir Ben-Shmuel,Rivka Dikstein
During translation initiation, eIF1A binds the ribosome through its N- and C-terminal tails, but the functional importance of this temporal interaction in mammalian cells is lacking. Using a high-throughput drug screen targeting eIF1A-RPS10 interaction, we identified inhibitors (1Ais) for eIF1A, RPS10, or both. Applying 1Ais in biochemical assays along specific and global translation experiments, we
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The microprotein C16orf74/MICT1 promotes thermogenesis in brown adipose tissue. EMBO J. (IF 9.4) Pub Date : 2025-05-12 Jennie Dinh,Danielle Yi,Frances Lin,Pengya Xue,Nicholas D Holloway,Ying Xie,Nnejiuwa U Ibe,Hai P Nguyen,Jose A Viscarra,Yuhui Wang,Hei Sook Sul
Brown and beige adipose tissues are metabolically beneficial for increasing energy expenditure via thermogenesis, mainly through UCP1 (uncoupling protein 1). Here, we identify C16orf74, subsequently named MICT1 (microprotein for thermogenesis 1), as a microprotein that is specifically and highly expressed in brown adipose tissue (BAT) and is induced upon cold exposure. MICT1 interacts with protein
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Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells. EMBO J. (IF 9.4) Pub Date : 2025-05-12 Esteban Quezada,Klaus-Peter Knoch,Jovana Vasiljevic,Annika Seiler,Akshaye Pal,Abishek Gunasekaran,Carla Münster,Daniela Friedland,Eyke Schöniger,Anke Sönmez,Pascal Roch,Carolin Wegbrod,Katharina Ganß,Nicole Kipke,Simon Alberti,Rita Nano,Lorenzo Piemonti,Daniela Aust,Jürgen Weitz,Marius Distler,Michele Solimena
Upregulation of insulin mRNA translation upon hyperglycemia in pancreatic islet β-cells involves several RNA-binding proteins. Here, we found that G3BP1, a stress granule marker downregulated in islets of subjects with type 2 diabetes, binds to insulin mRNA in glucose concentration-dependent manner. We show in mouse insulinoma MIN6-K8 cells exposed to fasting glucose levels that G3BP1 and its paralog
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YTHDC1 promotes postnatal brown adipose tissue development and thermogenesis by stabilizing PPARγ. EMBO J. (IF 9.4) Pub Date : 2025-05-12 Lihua Wang,Yuqin Wang,Kaixin Ding,Zhenzhi Li,Zhipeng Zhang,Xinzhi Li,Yue Song,Liwei Xie,Zheng Chen
Brown adipose tissue (BAT) plays a vital role in non-shivering thermogenesis and energy metabolism and is influenced by factors like environmental temperature, ageing, and obesity. However, the molecular mechanisms behind BAT development and thermogenesis are not fully understood. Our study identifies the m6A reader protein YTHDC1 as a crucial regulator of postnatal interscapular BAT development and
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Approaches to stable isotope tracing and in vivo metabolomics in the cancer clinic. EMBO J. (IF 9.4) Pub Date : 2025-05-12 Brandon Faubert,Alpaslan Tasdogan
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Annexin A5 controls VDAC1-dependent mitochondrial Ca2+ homeostasis and determines cellular susceptibility to apoptosis. EMBO J. (IF 9.4) Pub Date : 2025-05-09 Furkan E Oflaz,Alexander I Bondarenko,Michael Trenker,Markus Waldeck-Weiermair,Benjamin Gottschalk,Eva Bernhart,Zhanat Koshenov,Snježana Radulović,Rene Rost,Martin Hirtl,Johannes Pilic,Aditya Karunanithi Nivedita,Adlet Sagintayev,Gerd Leitinger,Bent Brachvogel,Susanne Summerauer,Varda Shoshan-Barmatz,Roland Malli,Wolfgang F Graier
Annexin A5 (AnxA5) is a Ca2+-dependent phospholipid-binding protein associated with the regulation of intracellular Ca2+ homeostasis. However, the precise role of AnxA5 in controlling mitochondrial Ca2+ signaling remains elusive. Here, we introduce a novel function of AnxA5 in regulating mitochondrial Ca2+ signaling. Our investigation revealed that AnxA5 localizes at and in the mitochondria and orchestrates
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Control of replication and gene expression by ADP-ribosylation of DNA in Mycobacterium tuberculosis. EMBO J. (IF 9.4) Pub Date : 2025-05-08 Rachel E Butler,Marion Schuller,Ritu Jaiswal,Jayanta Mukhopadhyay,Jim Barber,Suzie Hingley-Wilson,Emily Wasson,Alex Couto Alves,Ivan Ahel,Graham R Stewart
Mycobacterium tuberculosis maintains long-term infections characterised by the need to regulate growth and adapt to contrasting in vivo environments. Here we show that M. tuberculosis complex bacteria utilise reversible ADP-ribosylation of single-stranded DNA as a mechanism to coordinate stationary phase growth with transcriptional adaptation. The DNA modification is controlled by DarT, an ADP-ribosyltransferase
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CHD8 interacts with BCL11A to induce oncogenic transcription in triple negative breast cancer. EMBO J. (IF 9.4) Pub Date : 2025-05-06 Mark Waterhouse,Kyren Lazarus,Maria Francesca Santolla,Sara Pensa,Eleanor Williams,Abigail J Q Siu,Hisham Mohammed,Irina Mohorianu,Marcello Maggiolini,Jason Carroll,Laura S Itzhaki,Taufiq Rahman,Walid T Khaled
The identification of tumour-specific protein-protein interactions remains a challenge for the development of targeted cancer therapies. In this study we describe our approach for the identification of triple negative breast cancer (TNBC)-specific protein-protein interactions focusing on the oncogene BCL11A. We used a proteomic approach to identify the BCL11A protein networks in TNBC and compared it
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Fibroblast dynamics during mammary oncogenesis: senescence, Wnt9a and beyond. EMBO J. (IF 9.4) Pub Date : 2025-05-01 Viktoria Boeker,Raghu Kalluri
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Determining the effects of pseudouridine incorporation on human tRNAs. EMBO J. (IF 9.4) Pub Date : 2025-04-29 Anna D Biela,Jakub S Nowak,Artur P Biela,Sunandan Mukherjee,Seyed Naeim Moafinejad,Satyabrata Maiti,Andrzej Chramiec-Głąbik,Rahul Mehta,Jakub Jeżowski,Dominika Dobosz,Priyanka Dahate,Veronique Arluison,Frank Wien,Paulina Indyka,Michal Rawski,Janusz M Bujnicki,Ting-Yu Lin,Sebastian Glatt
Transfer RNAs (tRNAs) are ubiquitous non-coding RNA molecules required to translate mRNA-encoded sequence information into nascent polypeptide chains. Their relatively small size and heterogenous patterns of their RNA modifications have impeded the systematic structural characterization of individual tRNAs. Here, we use single-particle cryo-EM to determine the structures of four human tRNAs before
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Essential angiosperm-specific subunits of HDA19 histone deacetylase complexes in Arabidopsis. EMBO J. (IF 9.4) Pub Date : 2025-04-28 Na Liu,Jia-Xin Li,Dan-Yang Yuan,Yin-Na Su,Pei Zhang,Qi Wang,Xiao-Min Su,Lin Li,Haitao Li,She Chen,Xin-Jian He
Although the Arabidopsis thaliana RPD3-type histone deacetylase HDA19 and its close homolog HDA6 participate in SIN3-type histone deacetylase complexes, they display distinct biological roles, with the reason for these differences being poorly understood. This study identifies three angiosperm-specific HDA19-interacting homologous proteins, termed HDIP1, HDIP2, and HDIP3 (HDIP1/2/3). These proteins
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Altering metabolism programs cell identity via NAD+-dependent deacetylation. EMBO J. (IF 9.4) Pub Date : 2025-04-25 Robert A Bone,Molly P Lowndes,Silvia Raineri,Alba R Riveiro,Sarah L Lundregan,Morten Dall,Karolina Sulek,Jose A H Romero,Luna Malzard,Sandra Koigi,Indra J Heckenbach,Victor Solis-Mezarino,Moritz Völker-Albert,Catherine G Vasilopoulou,Florian Meier,Ala Trusina,Matthias Mann,Michael L Nielsen,Jonas T Treebak,Joshua M Brickman
Cells change their metabolic profiles in response to underlying gene regulatory networks, but how can alterations in metabolism encode specific transcriptional instructions? Here, we show that forcing a metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the early mammalian blastocyst in cultures. This shift in cellular
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Rbm24a dictates mRNA recruitment for germ granule assembly in zebrafish. EMBO J. (IF 9.4) Pub Date : 2025-04-25 Yizhuang Zhang,Jiasheng Wang,Hailing Fang,Shuqi Hu,Boya Yang,Jiayi Zhou,Raphaëlle Grifone,Panfeng Li,Tong Lu,Zhengyang Wang,Chong Zhang,Yubin Huang,Dalei Wu,Qianqian Gong,De-Li Shi,Ang Li,Ming Shao
The germ granules are ribonucleoprotein (RNP) biomolecular condensates that determine the fate of primordial germ cells (PGCs) and serve as a model for studying RNP granule assembly. Here, we show that the maternal RNA-binding protein Rbm24a is a key factor governing the specific sorting of mRNAs into germ granules. Mechanistically, Rbm24a interacts with the germ plasm component Buc to dictate the
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Inherent fast inactivation particle of Nav channels as a new binding site for a neurotoxin. EMBO J. (IF 9.4) Pub Date : 2025-04-22 Xi Zhou,Haiyi Chen,Shuijiao Peng,Yuxin Si,Gaoang Wang,Li Yang,Qing Zhou,Minjuan Lu,Qiaoling Xie,Xi He,Meijing Wu,Xin Xiao,Xiaoqing Luo,Xujun Feng,Wenxing Wang,Sen Luo,Yaqi Li,Jiaxin Qin,Minzhi Chen,Qianqian Zhang,Weijun Hu,Songping Liang,Tingjun Hou,Zhonghua Liu
Neurotoxins derived from animal venoms are indispensable tools for probing the structure and function of voltage-gated sodium (Nav) channels. Utilizing a novel centipede peptide toxin called rpTx1, we show that the "inherent inactivation particle" of Nav channels represents a binding site for a neurotoxin. The toxin comprises two functional domains: one for cell penetration and one for modulating Nav
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SDCBP/Syntenin-1 stabilizes BACH1 by disassembling the SCFFBXO22-BACH1 complex in triple-negative breast cancer. EMBO J. (IF 9.4) Pub Date : 2025-04-22 Phi-Long Tran,Okhwa Kim,Cheol Hwangbo,Hyo-Jin Kim,Young-Myeong Kim,Jeong-Hyung Lee
BACH1 is a redox-sensitive transcription factor facilitating tumor progression in triple-negative breast cancer (TNBC). However, the molecular mechanisms regulating BACH1 function in TNBC remain unclear. In this study, we demonstrate that SDCBP, a tandem-PDZ-domain protein, stabilizes BACH1 by disassembling the Skp1-Cullin1-FBXO22 (SCFFBXO22)-BACH1 complex via a heme/heme-oxygenase-1-independent manner
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Quantitative measures of clock protein dynamics in the mouse suprachiasmatic nucleus extends the circadian time-keeping model. EMBO J. (IF 9.4) Pub Date : 2025-04-17 Nicola J Smyllie,Alex A Koch,Antony D Adamson,Andrew P Patton,Adam Johnson,James S Bagnall,Olivia Johnson,Qing-Jun Meng,Andrew S I Loudon,Michael H Hastings
The suprachiasmatic nucleus (SCN) synchronises circadian rhythmicity (~24 h) across the body. The SCN cell-autonomous clock is modelled qualitatively as a transcriptional-translational feedback loop (TTFL), with heteromeric complexes of transcriptional activator and repressor proteins driving cyclical gene expression. How these proteins really behave within the SCN, individually and in relation to
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Oligomerised RIPK1 is the main core component of the CD95 necrosome. EMBO J. (IF 9.4) Pub Date : 2025-04-16 Nikita V Ivanisenko,Corinna König,Laura K Hillert-Richter,Maria A Feoktistova,Sabine Pietkiewicz,Max Richter,Diana Panayotova-Dimitrova,Thilo Kaehne,Inna N Lavrik
The necrosome is the key macromolecular signaling platform initiating necroptosis, i.e., a RIPK1/RIPK3-dependent program of cell death with an important role in the control of inflammation in multicellular organisms. However, the composition and structure of the necrosome remain incompletely understood. Here we use biochemical assays, quantitative mass spectrometry, and AlphaFold modeling to decipher
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Glutamylation of centrosomes ensures their function by recruiting microtubule nucleation factors. EMBO J. (IF 9.4) Pub Date : 2025-04-14 Shi-Rong Hong,Yi-Chien Chuang,Wen-Ting Yang,Chiou-Shian Song,Hung-Wei Yeh,Bing-Huan Wu,I-Hsuan Lin,Po-Chun Chou,Shiau-Chi Chen,Lohitaksh Sharma,Jui-Chen Lu,Rou-Ying Li,Ya-Chu Chang,Kuan-Ju Liao,Hui-Chun Cheng,Won-Jing Wang,Lily Hui-Ching Wang,Yu-Chun Lin
Centrosomes are tubulin-based organelles that undergo glutamylation, a post-translational modification that conjugates glutamic acid residues to tubulins. Although centrosomal glutamylation has been known for several decades, how this modification regulates centrosome structure and function remains unclear. To address this long-standing issue, we developed a method to spatiotemporally reduce centrosomal
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Fibroblast hierarchy dynamics during mammary gland morphogenesis and tumorigenesis. EMBO J. (IF 9.4) Pub Date : 2025-04-11 Rosa Pascual,Jinming Cheng,Amelia H De Smet,Bianca D Capaldo,Minhsuang Tsai,Somayeh Kordafshari,François Vaillant,Xiaoyu Song,Göknur Giner,Michael J G Milevskiy,Felicity C Jackling,Bhupinder Pal,Toby Dite,Jumana Yousef,Laura F Dagley,Gordon K Smyth,Naiyang Fu,Geoffrey J Lindeman,Yunshun Chen,Jane E Visvader
Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here, we have applied longitudinal single-cell transcriptome profiling of >45,000 fibroblasts in the mouse mammary gland across five different developmental stages and during oncogenesis. In the normal gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes
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Reconstruction of the ancient cyanobacterial proto-circadian clock system KaiABC. EMBO J. (IF 9.4) Pub Date : 2025-04-10 Silin Li,Zengxuan Zhou,Yufeng Wan,Xudong Jia,Peiliang Wang,Yu Wang,Taisen Zuo,He Cheng,Xiaoting Fang,Shuqi Dong,Jun He,Yilin Yang,Yichen Xu,Shaoxuan Fu,Xujing Wang,Ximing Qin,Qiguang Xie,Xiaodong Xu,Yuwei Zhao,Dan Liang,Peng Zhang,Qinfen Zhang,Jinhu Guo
Earlier in its history, the Earth used to spin faster than it does today. How ancient organisms adapted to the short day/night cycles during that time remains unclear. In this study we reconstruct and analyse the ancient circadian clock system KaiABC (anKaiABC) of cyanobacteria that existed ~0.95 billion years ago, when the daily light/dark cycle was ~18 h-long. Compared to their contemporary counterparts
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Ductal or Ngn3+ cells do not contribute to adult pancreatic islet beta-cell neogenesis in homeostasis. EMBO J. (IF 9.4) Pub Date : 2025-04-09 Xiuzhen Huang,Huan Zhao,Hui Chen,Zixin Liu,Kuo Liu,Zan Lv,Xiuxiu Liu,Ximeng Han,Maoying Han,Jie Lu,Qiao Zhou,Bin Zhou
The adult pancreatic ducts have long been proposed to contain rare progenitors, some of which expressing Ngn3, that generate new beta cells in endocrine-islet homeostasis. Due to their postulated rarity and the lack of definitive markers, the existence or absence of ductal endocrine progenitors remains unsettled despite many studies. Genetic lineage tracing of ductal cells or Ngn3+ cells with currently
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Temporal refinement of Dach1 expression contributes to the development of somatosensory neurons. EMBO J. (IF 9.4) Pub Date : 2025-04-09 Tünde Szemes,Alba Sabaté San José,Abdulkader Azouz,Maren Sitte,Gabriela Salinas,Younes Achouri,Sadia Kricha,Laurence Ris,Kristy Red-Horse,Eric J Bellefroid,Simon Desiderio
During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state. Several transcription factors in these cells follow a broad-to-restricted expression trajectory as development proceeds, giving rise to neuron subtypes with different identities. The relevance of this temporal refinement of transcription factor expression remains unclear as the functions of transcription
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Structural insights into small-molecule agonist recognition and activation of complement receptor C3aR. EMBO J. (IF 9.4) Pub Date : 2025-04-07 Jinuk Kim,Saebom Ko,Chulwon Choi,Jungnam Bae,Hyeonsung Byeon,Chaok Seok,Hee-Jung Choi
The complement system plays crucial roles in innate immunity and inflammatory responses. The anaphylatoxin C3a mediates pro-inflammatory and chemotactic functions through the G protein-coupled receptor C3aR. While the active structure of the C3a-C3aR-Gi complex has been determined, the inactive conformation and activation mechanism of C3aR remain elusive. Here we report the cryo-EM structure of ligand-free
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Updated values for Table 1 of fastest rubisco carboxylation rates in Davidi et al 2020. EMBO J. (IF 9.4) Pub Date : 2025-04-07 Yi-Chin Candace Tsai,Zhijun Guo,Ron Milo,Oliver Mueller-Cajar
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GAF-dependent chromatin plasticity determines promoter usage to mediate locust gregarious behavior. EMBO J. (IF 9.4) Pub Date : 2025-04-07 Xiao Li,Feng Jiang,Qing Liu,Zizheng Zhang,Wenjing Fang,Yutong Wang,Hongran Liu,Le Kang
Locusts, as devastating pests, can reversibly transform between solitary individuals and gregarious swarms with markedly different behaviors. Epigenetic regulation orchestrated by changes in chromatin openness modulates behavioral plasticity by controlling gene expression. However, the gene regulation mechanisms by which chromatin openness controls behavioral changes remain largely unknown. Here, we
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The selenocysteine-containing protein SELENOT maintains dopamine signaling in the midbrain to protect mice from hyperactivity disorder. EMBO J. (IF 9.4) Pub Date : 2025-04-07 Qing Guo,Zhao-Feng Li,Dong-Yan Hu,Pei-Jun Li,Kai-Nian Wu,Hui-Hui Fan,Jie Deng,Hong-Mei Wu,Xiong Zhang,Jian-Hong Zhu
Dopaminergic neuron dysfunction has been implicated in multiple neurological and psychiatric disorders. SELENOT is a selenocysteine-containing protein of the ER membrane with antioxidant and neuroprotective activities, but its pathophysiological role in dopaminergic neurons remains unclear. In this study we show that male mice with SELENOT-deficient dopaminergic neurons exhibit attention deficit/hyperactivity
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Nuclear envelope-associated lipid droplets are enriched in cholesteryl esters and increase during inflammatory signaling. EMBO J. (IF 9.4) Pub Date : 2025-04-07 Ábel Szkalisity,Lauri Vanharanta,Hodaka Saito,Csaba Vörös,Shiqian Li,Antti Isomäki,Teemu Tomberg,Clare Strachan,Ilya Belevich,Eija Jokitalo,Elina Ikonen
Cholesteryl esters (CEs) and triacylglycerols (TAGs) are stored in lipid droplets (LDs), but their compartmentalisation is not well understood. Here, we established a hyperspectral stimulated Raman scattering microscopy system to identify and quantitatively assess CEs and TAGs in individual LDs of human cells. We found that nuclear envelope-associated lipid droplets (NE-LDs) were enriched in cholesteryl
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Dimerization of GAS2 mediates crosslinking of microtubules and F-actin. EMBO J. (IF 9.4) Pub Date : 2025-04-01 Jiancheng An,Tsuyoshi Imasaki,Akihiro Narita,Shinsuke Niwa,Ryohei Sasaki,Tsukasa Makino,Ryo Nitta,Masahide Kikkawa
The spectraplakin family protein GAS2 was originally identified as a growth arrest-specific protein, and recent studies have revealed its involvement in multiple cellular processes. Its dual interaction with actin filaments and microtubules highlights its essential role in cytoskeletal organization, such as cell division, apoptosis, and possibly tumorigenesis. However, the structural basis of cytoskeletal
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The biochemical mechanism of Rho GTPase membrane binding, activation and retention in activity patterning. EMBO J. (IF 9.4) Pub Date : 2025-03-31 Michael C Armstrong,Yannic R Weiß,Lila E Hoachlander-Hobby,Ankit A Roy,Ilaria Visco,Alison Moe,Adriana E Golding,Scott D Hansen,William M Bement,Peter Bieling
Rho GTPases form plasma membrane-associated patterns that control the cytoskeleton during cell division, morphogenesis, migration, and wound repair. Their patterning involves transitions between inactive cytosolic and active membrane-bound states, regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). However
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SIRT5-mediated desuccinylation of PPA2 enhances HIF-1alpha-dependent adaptation to hypoxic stress and colorectal cancer metastasis. EMBO J. (IF 9.4) Pub Date : 2025-03-31 Xiang Zhang,Yuqin Di,Youpeng Wang,Jiale Qin,Lvlan Ye,Xiangqiong Wen,Zunfu Ke,Ziyang Wang,Weiling He
Metastasis is the primary cause of death in patients with colorectal cancer (CRC). Hypoxia is a hallmark of solid tumors that promotes cellular metabolic adaptation and dissemination. However, the mechanisms linking hypoxia-regulated metabolic adaptation to CRC metastasis remain unclear. Here, we found that inorganic pyrophosphatase 2 (PPA2) suppresses metastatic progression of CRC via its phosphatase
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HAND1 level controls the specification of multipotent cardiac and extraembryonic progenitors from human pluripotent stem cells. EMBO J. (IF 9.4) Pub Date : 2025-03-31 Adam T Lynch,Naomi Phillips,Megan Douglas,Marta Dorgnach,I-Hsuan Lin,Antony D Adamson,Zoulfia Darieva,Jessica Whittle,Neil A Hanley,Nicoletta Bobola,Matthew J Birket
Diverse sets of progenitors contribute to the development of the embryonic heart, but the mechanisms of their specification have remained elusive. Here, using a human pluripotent stem cell (hPSC) model, we deciphered cardiac and non-cardiac lineage trajectories in differentiation and identified transcription factors underpinning cell specification, identity and function. We discovered a concentration-dependent
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S-palmitoylation modulates ATG2-dependent non-vesicular lipid transport during starvation-induced autophagy. EMBO J. (IF 9.4) Pub Date : 2025-03-24 Wenhui Zheng,Maomao Pu,Sai Zeng,Hongtao Zhang,Qian Wang,Tao Chen,Tianhua Zhou,Chunmei Chang,Dante Neculai,Wei Liu
Lipid transfer proteins mediate the non-vesicular transport of lipids at membrane contact sites to regulate the lipid composition of organelle membranes. Despite significant recent advances in our understanding of the structural basis for lipid transfer, its functional regulation remains unclear. In this study, we report that S-palmitoylation modulates the cellular function of ATG2, a rod-like lipid
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A bacterial network of T3SS effectors counteracts host pro-inflammatory responses and cell death to promote infection. EMBO J. (IF 9.4) Pub Date : 2025-03-24 Hui Wen Yeap,Ghin Ray Goh,Safwah Nasuha Rosli,Hai Shin Pung,Cristina Giogha,Vik Ven Eng,Jaclyn S Pearson,Elizabeth L Hartland,Kaiwen W Chen
Innate immune signalling and cell death pathways are highly interconnected processes involving receptor-interacting protein kinases (RIPKs) as mediators of potent anti-microbial responses. However, these processes are often antagonised by bacterial type III secretion system (T3SS) effectors, and the cellular mechanisms by which the host retaliates are not completely understood. Here, we demonstrate
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A new hybrid post-translational modification-have you lost your (MARUb)les? EMBO J. (IF 9.4) Pub Date : 2025-03-20 Isaac de Araujo Matos,Nícolas Carlos Hoch
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A versatile toolbox for determining IRES activity in cells and embryonic tissues. EMBO J. (IF 9.4) Pub Date : 2025-03-13 Philipp Koch,Zijian Zhang,Naomi R Genuth,Teodorus Theo Susanto,Martin Haimann,Alena Khmelinskaia,Gun Woo Byeon,Saurabh Dey,Maria Barna,Kathrin Leppek
Widespread control of gene expression through translation has emerged as a key level of spatiotemporal regulation of protein expression. A prominent mechanism by which ribosomes can confer gene regulation is via internal ribosomal entry sites (IRESes), whose functions have however, remained difficult to rigorously characterize. Here we present a set of technologies in embryos and cells, including IRES-mediated
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Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation. EMBO J. (IF 9.4) Pub Date : 2025-03-10 Feng Yue,Lijie Gu,Jiamin Qiu,Stephanie N Oprescu,Linda M Beckett,Jessica M Ellis,Shawn S Donkin,Shihuan Kuang
During homeostasis and regeneration, satellite cells, the resident stem cells of skeletal muscle, have distinct metabolic requirements for fate transitions between quiescence, proliferation and differentiation. However, the contribution of distinct energy sources to satellite cell metabolism and function remains largely unexplored. Here, we uncover a role of mitochondrial fatty acid oxidation (FAO)
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Slik sculpts the plasma membrane into cytonemes to control cell-cell communication. EMBO J. (IF 9.4) Pub Date : 2025-03-06 Basile Rambaud,Mathieu Joseph,Feng-Ching Tsai,Camille De Jamblinne,Regina Strakhova,Emmanuelle Del Guidice,Renata Sabelli,Matthew J Smith,Patricia Bassereau,David R Hipfner,Sébastien Carréno
Cytonemes are signaling filopodia that facilitate long-range cell-cell communication by forming synapses between cells. Initially discovered in Drosophila for transporting morphogens during embryogenesis, they have since been identified in mammalian cells and implicated in carcinogenesis. Despite their importance, mechanisms controlling cytoneme biogenesis remain elusive. Here, we demonstrate that
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The green side of splicing: algal spliceosome shows remarkable structural conservation. EMBO J. (IF 9.4) Pub Date : 2025-03-06 Wojciech P Galej
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A double-agent microRNA regulates viral cross-kingdom infection in animals and plants. EMBO J. (IF 9.4) Pub Date : 2025-03-05 Wan Zhao,Hong Lu,Jiaming Zhu,Lan Luo,Feng Cui
Plant arbovirus infection is regulated by a delicate interplay between virus, vector, and host. While microRNAs are known to be transmitted across species, their role as cross-kingdom effectors in influencing arbovirus infectious cycles remains poorly understood. Our study reveals the dual role of miR-263a, a conserved insect microRNA, in governing rice stripe virus (RSV) infection within both insect
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p53 regulates DREAM complex-mediated repression in a p21-independent manner. EMBO J. (IF 9.4) Pub Date : 2025-03-04 Ritu Agrawal,Sagar Sengupta
The DREAM repressor complex regulates genes involved in the cell cycle and DNA repair, vital for maintaining genome stability. Although it mediates p53-driven repression through the canonical p53-p21-Rb axis, the potential for p53 to directly regulate DREAM targets independently of its transcriptional activity has not been explored. Here, we demonstrate that in asynchronously growing cells, p53 loss
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PLK1 inhibition delays mitotic entry revealing changes to the phosphoproteome of mammalian cells early in division. EMBO J. (IF 9.4) Pub Date : 2025-03-03 Monica Gobran,Antonio Z Politi,Luisa Welp,Jasmin Jakobi,Henning Urlaub,Peter Lenart
Polo-like kinase 1 (PLK1) is a conserved regulator of cell division. During mitotic prophase, PLK1 contributes to the activation of the cyclin-dependent kinase 1 (CDK1). However, the exact functions of PLK1 in prophase remain incompletely understood. Here, we show that PLK1 inhibition in synchronous G2 cell populations of multiple mammalian cell lines delays or prevents mitotic entry with high variability
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Competition for the nascent leading strand shapes the requirements for PCNA loading in the replisome. EMBO J. (IF 9.4) Pub Date : 2025-02-28 Emma E Fletcher,Morgan L Jones,Joseph T P Yeeles
During DNA replication, the DNA polymerases Pol δ and Pol ε utilise the ring-shaped sliding clamp PCNA to enhance their processivity. PCNA loading onto DNA is accomplished by the clamp loaders RFC and Ctf18-RFC, which function primarily on the lagging and the leading strand, respectively. RFC activity is essential for lagging-strand replication by Pol δ, but it is unclear why Ctf18-RFC is required
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Drosophila Alms1 proteins regulate centriolar cartwheel assembly by enabling Plk4-Ana2 amplification loop. EMBO J. (IF 9.4) Pub Date : 2025-02-28 Marine Brunet,Joëlle Thomas,Jean-André Lapart,Léo Krüttli,Marine H Laporte,Maria Giovanna Riparbelli,Giuliano Callaini,Bénédicte Durand,Véronique Morel
Centrioles play a central role in cell division by recruiting pericentriolar material (PCM) to form the centrosome. Alterations in centriole number or function lead to various diseases including cancer or microcephaly. Centriole duplication is a highly conserved mechanism in eukaryotes. Here, we show that the two Drosophila orthologs of the Alström syndrome protein 1 (Alms1a and Alms1b) are unexpected
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Ubiquitous MEIS transcription factors actuate lineage-specific transcription to establish cell fate. EMBO J. (IF 9.4) Pub Date : 2025-02-28 Zoulfia Darieva,Peyman Zarrineh,Naomi Phillips,Joshua Mallen,Araceli Garcia Mora,Ian Donaldson,Laure Bridoux,Megan Douglas,Sara F Dias Henriques,Dorothea Schulte,Matthew J Birket,Nicoletta Bobola
Control of gene expression is commonly mediated by distinct combinations of transcription factors (TFs). This cooperative action allows the integration of multiple biological signals at regulatory elements, resulting in highly specific gene expression patterns. It is unclear whether combinatorial binding is also necessary to bring together TFs with distinct biochemical functions, which collaborate
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Proton conductance by human uncoupling protein 1 is inhibited by purine and pyrimidine nucleotides. EMBO J. (IF 9.4) Pub Date : 2025-02-28 Scott A Jones,Alice P Sowton,Denis Lacabanne,Martin S King,Shane M Palmer,Thomas Zögg,Els Pardon,Jan Steyaert,Jonathan J Ruprecht,Edmund R S Kunji
Uncoupling protein 1 (UCP1, SLC25A7) is responsible for the thermogenic properties of brown adipose tissue. Upon fatty acid activation, UCP1 facilitates proton leakage, dissipating the mitochondrial proton motive force to release energy as heat. Purine nucleotides are considered to be the only inhibitors of UCP1 activity, binding to its central cavity to lock UCP1 in a proton-impermeable conformation
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Maintenance of p-eIF2α levels by the eIF2B complex is vital for colorectal cancer. EMBO J. (IF 9.4) Pub Date : 2025-02-27 Ivana Paskov Škapik,Chiara Giacomelli,Sarah Hahn,Hanna Deinlein,Peter Gallant,Mathias Diebold,Josep Biayna,Anne Hendricks,Leon Olimski,Christoph Otto,Carolin Kastner,Elmar Wolf,Christina Schülein-Völk,Katja Maurus,Andreas Rosenwald,Nikolai Schleussner,Rene-Filip Jackstadt,Nicolas Schlegel,Christoph-Thomas Germer,Martin Bushell,Martin Eilers,Stefanie Schmidt,Armin Wiegering
Protein synthesis is an essential process, deregulated in multiple tumor types showing differential dependence on translation factors compared to untransformed tissue. We show that colorectal cancer (CRC) with loss-of-function mutation in the APC tumor suppressor depends on an oncogenic translation program regulated by the ability to sense phosphorylated eIF2α (p-eIF2α). Despite increased protein synthesis
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Parasitic plasmids are anchored to inactive regions of eukaryotic chromosomes through a nucleosome signal. EMBO J. (IF 9.4) Pub Date : 2025-02-27 Fabien Girard,Antoine Even,Agnès Thierry,Myriam Ruault,Léa Meneu,Pauline Larrous,Mickaël Garnier,Sandrine Adiba,Angela Taddei,Romain Koszul,Axel Cournac
Natural plasmids are common in prokaryotes, but few have been documented in eukaryotes. The natural 2µ plasmid present in the yeast Saccharomyces cerevisiae is one of these best-characterized exceptions. This highly stable genetic element has coexisted with its host for millions of years, faithfully segregating at each cell division through a mechanism that remains unclear. Using proximity ligation
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An epitranscriptomic program maintains skeletal stem cell quiescence via a METTL3-FEM1B-GLI1 axis. EMBO J. (IF 9.4) Pub Date : 2025-02-27 Jing Wang,Weidong Liu,Tiantian Zhang,Manman Cui,Kexin Gao,Pengbo Lu,Shuxin Yao,Ziyan Cao,Yanbing Zheng,Wen Tian,Yan Li,Rong Yin,Jin Hu,Guoqiang Han,Jianfei Liang,Fuling Zhou,Jihua Chai,Haojian Zhang
Skeletal stem cells (SSCs) maintain the skeletal system via pluripotency and differentiation capacity. However, it remains largely unknown how these cells precisely regulate their function to maintain skeletal organization. Here, we delineate the RNA m6A modification landscape across skeletal cell populations in the mouse epiphysis. Our findings show that m6A modifications are prevalent in skeletal
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Francesco Amaldi (1939-2024) - a pioneer in RNA research. EMBO J. (IF 9.4) Pub Date : 2025-02-27 Irene Bozzoni
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Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose. EMBO J. (IF 9.4) Pub Date : 2025-02-25 Daniel S Bejan,Rachel E Lacoursiere,Jonathan N Pruneda,Michael S Cohen
The prevailing view on post-translational modifications (PTMs) is that a single amino acid is modified with a single PTM at any given time. However, recent work has demonstrated crosstalk between different PTMs, some occurring on the same residue. Such interplay is seen with ADP-ribosylation and ubiquitylation. For example, DELTEX E3 ligases were reported to ubiquitylate a hydroxyl group on free NAD+
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The structure of basal body inner junctions from Tetrahymena revealed by electron cryo-tomography. EMBO J. (IF 9.4) Pub Date : 2025-02-24 Sam Li,Jose-Jesus Fernandez,Marisa D Ruehle,Rachel A Howard-Till,Amy Fabritius,Chad G Pearson,David A Agard,Mark E Winey
The cilium is a microtubule-based eukaryotic organelle critical for many cellular functions. Its assembly initiates at a basal body and continues as an axoneme that projects out of the cell to form a functional cilium. This assembly process is tightly regulated. However, our knowledge of the molecular architecture and the mechanism of assembly is limited. By applying cryo-electron tomography, we obtained
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Modular in vivo assembly of Arabidopsis FCA oligomers into condensates competent for RNA 3' processing. EMBO J. (IF 9.4) Pub Date : 2025-02-24 Geng-Jen Jang,Alex L Payne-Dwyer,Robert Maple,Zhe Wu,Fuquan Liu,Sergio G Lopez,Yanning Wang,Xiaofeng Fang,Mark C Leake,Caroline Dean
Our understanding of the functional requirements underpinning biomolecular condensation in vivo is still relatively poor. The Arabidopsis RNA binding protein FLOWERING CONTROL LOCUS A (FCA) is found in liquid-like nuclear condensates that function in transcription termination, promoting proximal polyadenylation at many target genes in the Arabidopsis genome. To further understand the properties of
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A one-two punch against cancer: combining CDK4 inhibitors with lysosomotropic agents. EMBO J. (IF 9.4) Pub Date : 2025-02-24 Gerardo Ferbeyre
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Decoding host-microbe interactions with engineered human organoids. EMBO J. (IF 9.4) Pub Date : 2025-02-21 Lucas A Meirelles,Alexandre Persat